POS0434 CCL20 INHIBITION AMELIORATES PERIPHERAL ARTHRITIS IN ANKYLOSING SPONDYLITIS
Authors: Y. W. Park, H. J. Kim, Y. J. Lee, M. J. Kim, H. I. Lee, S. C. Shim, S. Jo, T. H. Kim, E. J. Won, T. J. Kim
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Ankylosing spondylitis (AS) is a rheumatic disease characterized by chronic inflammation. Several lines of evidence implicate interleukin (IL)-17A-secreting T helper (Th)17 cells in AS pathogenesis. One of the receptors of Th17 cell, C-C motif chemokine ligand 20 (CCL20) is known to attract C-C chemokine receptor 6 (CCR6) expressing cells to the site of inflammation. However, the role and mechanisms of CCL20 in AS are not well understood. <h3>Objectives</h3> Therefore, this study aimed to evaluate the function of CCL20 in patients with AS. <h3>Methods</h3> Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were obtained from AS patients. Inflammatory cytokine-producing cells were analyzed using flow cytometry and enzyme-linked immunosorbent assay (ELISA). To determine the direct effect of cell migration in the presence of CCL20, a transwell migration assay was performed. In in vivo experiments, SKG mice were treated with either CCL20 blocking antibody or isotype control antibody. Clinical signs of mice were monitored twice a week and scored by two independent observers. At the experimental endpoint, specimens of the ankle was obtained from mice. Two blinded readers then performed pathological scoring for arthritis using immunohistochemistry. <h3>Results</h3> IL-17A producing cells were significantly higher expressed in SFMCs of AS patients than in PBMCs of AS or healthy controls. CCL20-positive cells showed significantly increased IL-17A production than CCL20-negative cells. To confirm the relationship between CCL20 and IL-17A production, IL-17A expression was observed with either CCL20 agonist or antagonist. Treatment with CCL20 agonist showed an increase in IL-17A in PBMCs from AS patients. Meanwhile decreasing IL-17A level was observed in SFMCs from AS patients when treated with CCL20 inhibitors. In cell migration assay experiments, cell migration increased when CCL20 was added to the CD4-positive cells. In an vivo model, CCL20 inhibitors significantly suppressed arthritis symptoms (Figure 1). In addition, histologic evaluation showed that mice treated with CCL20 inhibitor had lower arthritis scores than isotype-treated control mice. <h3>Conclusion</h3> This study demonstrates CCL20 blockade improved joint inflammation in AS. Therefore, CCL20-target therapy could be a promising treatment for AS. <h3>References</h3> [1]Taurog, J.D., A. Chhabra, and R.A. Colbert, <i>Ankylosing Spondylitis and Axial Spondyloarthritis.</i> N Engl J Med, 2016. <b>375</b>(13): p. 1303. [2]Watad, A., et al., <i>The Early Phases of Ankylosing Spondylitis: Emerging Insights From Clinical and Basic Science.</i> Front Immunol, 2018. <b>9</b>: p. 2668. [3]Lee, Y., et al., <i>Induction and molecular signature of pathogenic TH17 cells.</i> Nat Immunol, 2012. <b>13</b>(10): p. 991-9. [4]Yasuda, K., Y. Takeuchi, and K. Hirota, <i>The pathogenicity of Th17 cells in autoimmune diseases.</i> Semin Immunopathol, 2019. <b>41</b>(3): p. 283-297. [5]Hu, J., et al., <i>C-C motif chemokine ligand 20 regulates neuroinflammation following spinal cord injury via Th17 cell recruitment.</i> J Neuroinflammation, 2016. <b>13</b>(1): p. 162. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.